tbuckley/cabot-search huggingface dataset:
Abstract 12537: Sedentary Behavior is a Stronger Risk Factor Than Diabetes for Incident Peripheral Artery Disease: Data From the Henry Ford Exercise Testing (FIT) Project
Authors: Jonathan K Ehrman, Steven J Keteyian, Herbert D Aronow, Syed Ahsan, Michael J Blaha, Mouaz H Al-Mallah, Clinton A Brawner
Journal: Circulation (2023)

Introduction: Age, diabetes (DM) and smoking are risk factors related to developing peripheral artery disease (PAD). Little is known about the strength of the association of sedentary behavior (SB) or fitness relative to traditional risk factors, and the risk of PAD. Hypothesis: SB and fitness are independently related to risk of PAD, but their relative contribution is less than DM and smoking. Methods: We assessed 41,268 patients (pts) (age= 55±12 yr, 51% male, 64% white) from the Henry Ford Exercise Testing (FIT) who completed a clinically ordered exercise stress test between January 1991 and June 2009. Fitness (metabolic equivalents of task, METs) was estimated from peak treadmill speed and grade. Patients were asked about current exercise habits and coded as sedentary if not performing regular aerobic mode exercise. Patient self-report and medical records were used to determine smoking history and DM. Those with established PAD at the time of testing were excluded. ICD9 codes 440.XX and 443.9 identified first incidence of PAD from test date up to June 2010. Using multivariable Cox regression (Wald X 2 , α &lt;0.05) we report on the top 5 predictors of time to incident PAD in ALL pts and stratified by race. Results: During a median follow-up of 7.1 yr (IQR 4.2-11.1 yr) there were 2,596 (6%) incident diagnoses of PAD. Wald X 2 values were rank ordered (Table). SB and fitness were independently related to time to incident PAD. SB ranked the 3 rd strongest variable for both ALL (HR=2.5 [2.2, 2.9]) and WHITE pts (HR=2.5 [2.1, 2.9]). For BLACK pts SB ranked 2 nd (HR=2.7 [2.1, 3.6]), above DM and smoking. Fitness ranked 5 th for ALL and BLACK pts, and 6 th in WHITE pts. Conclusion: In ALL pts, and WHITE and BLACK pts separately, SB was strongly associated with time to incident PAD, and explained more of the variation in incident PAD than DM. In BLACK pts SB was also stronger than smoking. Further research is needed to clarify the role of SB as a potential emerging modifiable risk factor for the development of PAD.
The heterogeneity and complexity of skin surface lipids in human skin health and disease
Authors: Dalibor Mijaljica, Joshua P. Townley, Fabrizio Spada, Ian P. Harrison
Journal: Progress in Lipid Research (2023)

The outermost epidermal layer of the skin, the stratum corneum, is not simply a barrier that safeguards skin integrity from external insults and invaders, it is also a delicately integrated interface composed of firm, essentially dead corneocytes and a distinctive lipid matrix. Together, the stratum corneum lipid matrix and sebum lipids derived from sebaceous glands give rise to a remarkably complex but quite unique blend of skin surface lipids that demonstrates tremendous heterogeneity and provides the skin with its indispensable protective coating. The stratum corneum lipid matrix is composed primarily of three major lipid classes: ceramides, non-esterified fatty acids and cholesterol, whereas sebum is a waxy mixture predominantly composed of acylglycerols, wax esters, non-esterified fatty acids, squalene, cholesterol and cholesterol esters. The balance of these skin surface lipids in terms of their relative abundance, composition, molecular organisation and dynamics, and their intricate interactions play a crucial role in the maintenance of healthy skin. For that reason, even minuscule alterations in skin surface lipid properties or overall lipid profile have been implicated in the aetiology of many common skin diseases including atopic dermatitis, psoriasis, xerosis, ichthyosis and acne. Novel lipid-based interventions aimed at correcting the skin surface lipid abnormalities have the potential to repair skin barrier integrity and the symptoms associated with such skin diseases, even though the exact mechanisms of lipid restoration remain elusive.
Abstract 13886: Impaired Locomotor Muscle Blood Flow During Cycling Exercise in Heart Failure With Preserved Ejection Fraction
Authors: Gizem Cifci, Shane Hammer, Eric Bruhn, Thomas Bissen, Barry A Borlaug, Thomas P Olson, Joshua R Smith
Journal: Circulation (2023)

Introduction: Obesity and hypertension (HTN) are highly prevalent comorbid risk factors for heart failure with preserved ejection fraction (HFpEF). Obesity and HTN independently increase sympathetic nervous activity and impair muscle blood flow during exercise. Previous work has reported attenuated limb blood flow in patients with HFpEF; however, these findings were compared to controls with dissimilar comorbidities and during small muscle mass exercise. It is unclear if HFpEF alters muscle blood flow responses independent of the obesity- and HTN-mediated alterations. Hypothesis: We hypothesized the muscle blood flow response during cycling would be lower in HFpEF patients than age, sex, BMI, and HTN matched controls (CTL). Methods: HFpEF patients (n=14, 9M/5W, 71±7yrs, 32±4 kg/m 2 ) and CTL (n=12, 8M/4W, 69±7yrs, 31±4 kg/m 2 ) performed an incremental cycling test. Blood pressure was measured by manual sphygmomanometry, cardiac output (Q) by open-circuit acetylene wash-in technique, and systemic vascular resistance (SVR) was calculated. Vastus lateralis blood flow index (BFI) was measured by near-infrared spectroscopy and indocyanine green dye injections and venous norepinephrine concentration was measured. Changes from rest to 40 W of the incremental test are reported. Results: Resting Q, mean arterial pressure, SVR, and venous norepinephrine concentration were not statistically different between groups (p&gt;0.18). From rest to 40 W, the increases in Q (CTL: 3.9±0.8 vs. HFpEF: 3.6±0.7 L/min), mean arterial pressure (CTL: 5.7±2.7 vs. HFpEF: 6.6±6.1 mmHg), and SVR (CTL: -7.3±2.1 vs. HFpEF: -6.0±2.0 mmHg/L/min) were not statistically different between groups (all, p&gt;0.13). The HFpEF group had smaller increases in vastus lateralis BFI at 40 W compared to CTL (CTL: 7.2±3.6 vs. HFpEF: 4.2±2.6 fold-increase from rest) (p=0.02). The HFpEF group had greater increases in venous norepinephrine concentration from rest to 40 W than CTL (CTL: 164±216 vs. HFpEF: 377±247 pg/mL) (p=0.05). Conclusions: Our findings suggest that, compared to age, sex, BMI, and HTN matched controls, patients with HFpEF have an impaired locomotor muscle blood flow response during submaximal cycling exercise likely due to higher locomotor muscle vascular resistance.
Abstract 12571: Factors That Predict Longitudinal Transition of Symptom Cluster Profiles in Heart Failure
Authors: Zequan Wang, Nancy S Redeker, Stephen Walsh, Christine Tocchi, Kyounghae Kim, Deborah A Chyun
Journal: Circulation (2023)

Background: Symptom trajectories in people with heart failure (HF) can vary over time. Few studies have explored how symptom clusters transition, essential to determine interventions. Aims: (1) Describe transitions in symptom cluster profiles in people with HF over 8 years; (2) Identify factors predicting the transitions. Methods: We conducted secondary analysis of data from the 2008, 2012, and 2016 surveys of the Health and Retirement Study (HRS), using latent transition analysis to identify cluster profiles (fatigue, dyspnea, pain, swelling, depressive symptoms, dizziness), and multinomial regression to determine the predictive factors. Results: HRS included 690 HF subjects (57% female; mean age=74.9 (SD =10.04) years). Four cluster profiles were identified: high burden, low burden, distressing, and respiratory-depressive distress. The probability staying in the same profile ranged from 0.60 to 0.89. Male sex (OR=1.39; 95% CI=0.92, 1.82), black race (OR=1.92; 95% CI=1.37, 2.73), smoking (OR=2.44; 95% CI=1.56, 3.71), having diabetes (OR=3.99; 95% CI=2.90, 6.27) and lung disease (OR=1.40; 95% CI=0.83, 1.68) were associated with an increased odds of moving from the distressing to the high burden profile. Smoking (OR=1.17; 95% CI=0.66, 1.55), having arthritis (OR=4.44; 95% CI=2.80, 6.33), lung disease (OR=1.72; 95% CI=1.17, 2.49), and diabetes (OR=3.84; 95% CI=2.87, 5.94) were associated with an increased odds of moving from the respiratory-depressive distress to the high burden profile. Black race (OR=3.58; 95% CI=2.80, 6.20), smoking (OR=1.44; 95% CI=0.91, 2.10), having arthritis (OR=1.71; 95% CI= 1.20, 2.59), lung disease (OR=1.30; 95% CI= 0.55, 1.95), and diabetes (OR=1.81; 95% CI=1.34, 2.90) were associated with an increased odds of moving from the low burden to the distressing profile. Male sex (OR=2.13; 95% CI= 1.66, 3.68), having arthritis (OR=1.51; 95% CI=1.15, 2.13) and lung disease (OR=2.28; 95% CI=1.57, 4.34) were associated with an increased odds of moving from the low burden to the respiratory-depressive distress profile. Conclusions: Although symptom cluster profiles remained stable, transitions were observed, and deterioration can occur. The identified predictive factors may enhance long-term symptom management.
Abstract 12554: Machine Learning-Based Detection of Intraoperative Ischemia Utilizing the VitalDB Database
Authors: Iqram Hussain, Balaji Pandian, Julianna Zeepvat, Antonis A Armoundas, Richard Boyer
Journal: Circulation (2023)

Introduction: Myocardial ischemia, characterized by insufficient blood supply to the heart, is a critical condition often associated with adverse cardiac events, including myocardial infarction. Detecting intraoperative ischemia holds substantial clinical significance. This study aims to develop a machine-learning (ML) model to detect intraoperative hypotension as a marker of ischemia using electrocardiogram (ECG) features. Hypothesis: We hypothesize that machine-learning algorithms can detect changes in ECG episodes during ischemic or subischemic events associated with prolonged hypotension. Methods: The study utilized the VitalDB database, a comprehensive repository of intraoperative data of 6,388 patients, including ECG recordings and other vital signs. The ML model was a binary classifier of a hypotensive event (MBP &lt;65 mm Hg) or a non-hypotensive event (MBP &gt;75 mm Hg) by analyzing ECG-II and ECG-V5 waveforms. We extracted relevant ECG features such as ST-deviation (ST-elevation or ST-depression), as clinical indicators of myocardial ischemia. The adaptive boosting (AdaBoost), Gradient boosting (GB), and Extreme gradient boosting (XGB) methods, ML boosting techniques, were employed to develop a hypotension predictive model for detecting ischemic episodes. The primary outcomes were the accuracy and the area under the receiver operating characteristic (AUROC) curve. Additionally, we utilized the Shapley Additive Explanations (SHAP) to determine the contribution of the ECG features to the ML model. Results: The GB machine learning model exhibited the best results (Accuracy: 89%, AUROC: 0.92) in predicting hypotensive events. Furthermore, the model achieved high sensitivity and specificity in identifying ischemic episodes. SHAP analysis revealed that ST-deviation is the most significant contributing ECG feature in predicting intraoperative hypotension. Conclusions: These results demonstrate the potential utility of ML-based identification of ECG features in accurately identifying ischemic episodes. Implementation of an improved diagnostic methodology for intraoperative ischemia detection can have a significant impact on patient care, enhancing patient safety and improving surgical outcomes.
Abstract 12536: Occurrence of New-Onset Atrial Fibrillation in Patients After Left Atrial Appendage Closure
Authors: Sakshum Chadha, Sahityasri Thapi, Abhishek Maan, Iwanari Kawamura, Brandon Needelman, Richa Patel, Paurush Ambesh, Daniel Musikantow, Mohit Turagam, William Whang, Marc Miller, Srinivas Dukkipati, Vivek Y Reddy
Journal: Circulation (2023)

Introduction: Left atrial appendage closure (LAAC) has evolved as a non-pharmacological alternative for stroke prevention in patients with Atrial fibrillation (AF). The occurrence of post-operative AF is well described after cardiac and percutaneous procedures. But, there is limited understanding of the possibility of new-onset AF as a result of LAAC. Aims: To investigate the incidence of, and factors associated with, AF after LAAC. Methods: We conducted a retrospective analysis of 121 patients with i) paroxysmal AF, 2) had undergone LAAC, and 3) had an implantable electronic devices (CIEDs): pacemaker, defibrillator or implantable loop recorder. Patients with persistent AF and those presenting in AF on the day of LAAC were excluded. Data were collected on baseline characteristics, Colchicine use, antiarrhythmic drugs and prior history of AF ablation. Remote transmissions and device interrogations were analyzed to ascertain new-onset AF during the 6 months follow up period after LAAC. Univariate and multivariable analyses were performed to analyze factors associated with the occurrence of AF after LAAC. Results: Of the total 121 patients, 39 (32.2%) developed AF during the 6 month follow up period after LAAC. On univariate analysis, a lower CHA2DS2-Vasc score was associated with a lower incidence of AF post LAAC (OR 0.74, 95% CI 0.55-0.98, p = 0.04). On multivariable analysis, including variables of age, gender, CHA2DS2-Vasc score, use of Colchicine and history of AF Ablation, we observed a statistical trend towards the protective effect of prior AF ablation on occurrence of AF after LAAC (adjusted OR 0.32, 95% CI 0.10-1.05, p =0.06). There was also a statistical trend towards the protective effect of Colchicine on occurrence of AF after LAAC (adjusted OR 0.15, 95% CI 0.02-1.29, p =0.08). Conclusions: In our study of paroxysmal AF patients undergoing LAAC, who presented in sinus rhythm on the day of the procedure, the incidence of CIED detected post-procedural AF was 32.2%. We observed statistical trends towards protective effects of prior AF Ablation and use of Colchicine during the peri-LAAC period on occurrence of AF after LAAC.
Abstract 12547: Incidence of Pulmonary Hypertension in the Echocardiographic Referral Population
Authors: Jonah D Garry, Suman Kundu, Jeffrey Annis, Charles Alcorn, Svetlana Eden, Emily K Smith, Bradley A Maron, Matthew S Freiberg, Evan Brittain
Journal: Circulation (2023)

Background: Incident rates (IRs) for pulmonary hypertension (PH) using diagnostic data rather than diagnostic codes (DC) have not been reported. We examined PH IRs, risk factors, and mortality among patients (pts) referred for echocardiography (TTE) in a national healthcare system and a separate tertiary care center. Methods: Pulmonary artery systolic pressure (PASP) estimates were extracted from the Veterans Affairs (1999-2020) and Vanderbilt (1994-2020) systems. PH was defined as PASP &gt;35 mmHg. Individuals free of PH at baseline were followed through incident PH, death, or censored at end of study. Secondary outcome was mortality rate (MR) after incident PH. We used Poisson regression to estimate IRs and cox models for hazard ratios. Results: We identified 245,067 veterans (60 years [IQR 55-64], 94% male, 20% Black) and 117,526 VUMC pts (60 years [IQR 46-70], 46% male, 11% Black) free of PH at baseline. Only 22% of pts with TTE-based PH had a DC for PH. PH IRs and adjusted hazard were substantially higher in pts with HF or COPD and highest in pts with both ( Table 1 ). MR after incident PH was highest in pts with both HF and COPD and lowest in pts without either (Figure 1A ). MRs increased markedly at PASP values &gt;45mmHg ( Figure 1B ). Independent risk factors for incident PH included older age (HR 1.07; 95%CI 1.06-1.09), male sex (HR 1.24; 95%CI 1.17-1.30), black race (HR 1.10; 95%CI 1.07-1.13), and cardiometabolic comorbidities. Conclusions: PH IRs estimated by raw diagnostic data are higher than DC-based IRs and strongly associated with HF and COPD. PASP &gt;45mmHg at the time of incident PH is associated with high mortality.
Abstract 16911: Timing of Initiation of Extracorporeal Membrane Oxygenation Support and Outcomes Among Patients With Cardiogenic Shock
Authors: Jacob C Jentzer, Stavros G Drakos, Craig Selzman, Clark G Owyang, Felipe Teran, Joseph Tonna
Journal: Circulation (2023)

Introduction: Venoarterial extracorporeal membrane oxygenation (VA ECMO) provides full hemodynamic support for cardiogenic shock (CS), but optimal timing of ECMO initiation remains uncertain. Hypothesis: We hypothesized that earlier initiation of ECMO would be associated with improved survival in CS patients. Methods: We analyzed adult patients with CS who received VA ECMO from the Extracorporeal Life Support Organization (ELSO) Registry from 2009 - 2019, excluding those cannulated following an operation. Multivariable logistic regression evaluated the association between time from admission to ECMO initiation and in-hospital mortality. Results: Among 8619 patients (median 56.7 years; 33.5% females), the duration from admission to ECMO initiation was 14 (5, 32) hours. Patients who had ECMO initiated within 24 hours (n = 5882 [68.2%]) differed from those who had ECMO initiated after 24 hours, with younger age, more preceding cardiac arrest, and worse acidosis. After adjustment, patients with ECMO initiated more than 24 hours after admission had higher risk of adjusted in-hospital mortality (adjusted OR 1.20, 95% CI 1.06-1.36, p = 0.004) (Figure 1). Each 12-hour increase in the time from admission to ECMO initiation was incrementally associated with higher adjusted in-hospital mortality (adjusted OR 1.06, 95% CI 1.03-1.10, p &lt; 0.001). The association between longer time to ECMO and worse outcomes appeared stronger in patients with lower shock severity. Among patients who were cannulated within 24 hours, those cannulated during the same day shift had lower mortality than those who were admitted at night and cannulated the following day (adjusted OR adjusted OR 0.81, 95% CI 0.66-0.99, p = 0.04). Conclusions: Longer delays from admission to ECMO initiation were associated with higher mortality in a large-scale, international registry. Our analysis supports optimization of door-to-support time and the avoidance of inappropriately delayed ECMO initiation.
Abstract 12558: Sodium-Glucose Cotransporter-2 Inhibitor Quality Improvement Initiative for Guideline-Directed Medical Therapy in Heart Failure (SQUAD-HF)
Authors: Kashvi Gupta, Preetham Gunta, John Spertus, Andrew J Sauer
Journal: Circulation (2023)

Introduction: Despite efforts encouraging SGLT2i prescriptions at discharge for decompensated heart failure (HF), recent data suggest only 1 in 5 patients receive them with a median odds ratio of 2.5 across hospitals. One of the reasons for under prescription of SGLT2i is cost. Aim: We implemented a comprehensive quality improvement initiative, focusing on education and care coordination, at 2 hospitals, to reduce financial barriers to initiation of SGLT2i prior to discharge. Methods: Interventions were implemented between October 2022 and January 2023. The education component of the intervention included providing residents, fellows, and faculty information regarding the latest HF guidelines, drug profile, and insurance coverage of SGLT2i through multiple modalities like grand rounds, posters, memes, and a dedicated website with links to published research. The care-coordination component of the intervention included similar presentations to pharmacists, social workers, and care coordinators. Best practices including cost checking of SGLT2i earlier during inpatient stay were encouraged throughout the study period. Primary outcome was a change in physician-reported financial barriers to prescription of SGLT2i assessed by a 10-item survey before and after the interventions. Results: Pre- and post-intervention surveys were completed by 82 and 56 healthcare providers; 52% were residents, 8% cardiology fellows, 16% internal medicine attendings, 14% cardiology attendings, and 8% cardiology nurse practitioners respectively. Physicians reported an 18.7% reduction in access and affordability barriers to prescribing SGLT2i for patients admitted with HF, from 86.6% to 67.9% (Table 1). Conclusion: Through a comprehensive education initiative and improving care coordination tailored to the health systems, SQUAD-HF reduced physician-reported access and affordability barriers to SGLT2i prescription prior to discharge for patients admitted with HF.
Abstract 19181: MicroRNA Regulation of Adipose Browning and Glucose Uptake Improves Cardiometabolic Disease
Authors: Furkan Bestepe, Colette M Fritsche, Sarah Persing, Brooke Ruemmele, Sarah Powers, Abhishek Chatterjee, Gordon Huggins, Basak Icli
Journal: Circulation (2023)

The prevalence of obesity is on the rise worldwide. Brown adipose tissue (BAT), a highly vascularized organ, is activated in response to cold temperatures to generate heat and modulate metabolic efficiency. MicroRNAs (miRNAs) are small, noncoding RNAs that are implicated in cardiometabolic disease. However, relevant miRNAs in the endothelium of the microvasculature of BAT, how they crosstalk to the surrounding adipose tissue in cardiometabolic disease is not fully understood. We profiled microRNAs from the endothelial cells (ECs) of brown adipose tissue (BAT) of mice with diet-induced obesity (DIO) using microRNA-Seq and identified microRNA-485-5p ( miR-485 ) as one of the most differentially regulated miRNAs compared to the chow control. MiR-485 expression was rapidly induced in ECs in response to glucose (2.2-fold) and palmitate (1.63-fold). Loss-of-function studies revealed that neutralization of miR-485 increased glucose uptake to 3T3-L1 adipocytes and human adipose organoids co-cultured with conditioned media from ECs deficient in miR-485 ; while also increasing the mRNA and protein expression of brown fat marker, UCP1. Multiplex ELISA analyses of conditioned media from ECs overexpressing miR-485 showed a significant decrease in the release of IL-25 from ECs (22.5%) while the inhibition of miR-485 in ECs increased IL-25 release by 36.3%. Interestingly, IL-25 increased glucose uptake to 3T3-L1 adipocytes. Systemic intravenous delivery of LNA-anti-miR-485 inhibitor increased expression of UCP1 (31.4%) in BAT by confocal immunofluorescence, improved BAT function as measured by multispectral optoacoustic tomography (MSOT), while improving glucose tolerance and insulin resistance by 10.2% and 14.2% respectively. Metabolic profiling revealed increased energy expenditure (25%), decreased respiratory exchange rate (6%), and increased left ventricular ejection fraction (LVEF) (9.5%). The global longitudinal strain was higher by 28% compared to control mice with DIO. Our findings indicate that miR-485 plays a key regulatory role in controlling adipose browning and metabolism in an EC-paracrine mediated crosstalk in DIO, an effect that could be exploited for therapeutic intervention in obesity-induced cardiometabolic disease.